A Viral Protein Mediates Superinfection Exclusion at the Whole-Organism Level but Is Not Required for Exclusion at the Cellular Level
A Viral Protein Mediates Superinfection Exclusion at the Whole-Organism Level but Is Not Required for Exclusion at the Cellular Level
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DOI：
10.1128/jvi.01612-14
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发表时间：
2014-10-01
影响因子：
5.4
通讯作者：
Folimonova, Svetlana Y.
中科院分区：
文献类型：
--
作者：
Bergua, Maria;Zwart, Mark P.;Folimonova, Svetlana Y.
重复感染排除（SIE），即已建立的病毒感染干扰由相同或密切相关的病毒引起的继发感染的能力，已被描述用于不同的病毒，包括人类、动物和植物的重要病原体。柑橘衰退病毒（Citrus tristeza virus，CTV）是一种正义RNA病毒，由于存在几种不同的病毒株，是研究SIE的一个有价值的模式系统。此外，CTV允许在整个生物体水平上检查SIE。以前，我们证明了CTV的SIE是一种病毒控制的功能，需要病毒蛋白p33。在这项研究中，我们表明，p33介导的SIE在整个生物体水平，而它是不需要排除在细胞水平。用荧光蛋白标记的CTV变体缺乏p33的宿主的原发感染不干扰用不同荧光蛋白标记的相同病毒的继发感染的建立。然而，两种病毒的细胞共感染是罕见的。所获得的观察结果，沿着细胞感染复数（MOI）和MOI模型选择的估计，表明低水平的细胞共感染似乎是最好的解释在细胞水平上的排斥。基于这些结果，我们提出，由CTV的SIE是在两个层面上的细胞和整个有机体的水平，由两个不同的机制，可以独立运作。病毒SIE的这一新的方面突出了这一现象的有趣的复杂性，进一步了解这一点可能会开辟新的途径，以管理病毒疾病。重要的是，许多病毒表现出超感染排斥（SIE），建立病毒感染的能力，以干扰相关病毒的继发感染。SIE在病毒种群的致病和进化中起着重要作用。这里描述的观察结果表明，SIE可以在宿主的不同水平上独立控制：整个生物体水平或单个细胞水平。柑橘衰退病毒（CTV）的p33蛋白，RNA病毒，被证明介导的SIE在整个生物体水平，而它似乎是不需要在细胞水平上的排斥。因此，CTV的SIE是高度复杂的，并且似乎使用与其他病毒不同的机制。对这一现象的更好理解可能会导致控制人类和农业生态系统中病毒性疾病的新战略的发展。
Superinfection exclusion (SIE), the ability of an established virus infection to interfere with a secondary infection by the same or a closely related virus, has been described for different viruses, including important pathogens of humans, animals, and plants. Citrus tristeza virus (CTV), a positive-sense RNA virus, represents a valuable model system for studying SIE due to the existence of several phylogenetically distinct strains. Furthermore, CTV allows SIE to be examined at the whole-organism level. Previously, we demonstrated that SIE by CTV is a virus-controlled function that requires the viral protein p33. In this study, we show that p33 mediates SIE at the whole-organism level, while it is not required for exclusion at the cellular level. Primary infection of a host with a fluorescent protein-tagged CTV variant lacking p33 did not interfere with the establishment of a secondary infection by the same virus labeled with a different fluorescent protein. However, cellular coinfection by both viruses was rare. The obtained observations, along with estimates of the cellular multiplicity of infection (MOI) and MOI model selection, suggested that low levels of cellular coinfection appear to be best explained by exclusion at the cellular level. Based on these results, we propose that SIE by CTV is operated at two levels-the cellular and the whole-organism levels-by two distinct mechanisms that could function independently. This novel aspect of viral SIE highlights the intriguing complexity of this phenomenon, further understanding of which may open up new avenues to manage virus diseases.IMPORTANCEMany viruses exhibit superinfection exclusion (SIE), the ability of an established virus infection to interfere with a secondary infection by related viruses. SIE plays an important role in the pathogenesis and evolution of virus populations. The observations described here suggest that SIE could be controlled independently at different levels of the host: the whole-organism level or the level of individual cells. The p33 protein of citrus tristeza virus (CTV), an RNA virus, was shown to mediate SIE at the whole-organism level, while it appeared not to be required for exclusion at the cellular level. SIE by CTV is, therefore, highly complex and appears to use mechanisms different from those proposed for other viruses. A better understanding of this phenomenon may lead to the development of new strategies for controlling viral diseases in human populations and agroecosystems.